In vivo 31P NMR studies of paraplegics' muscles activated by functional electrical stimulation

The bioenergetics of paralyzed muscles of spastic paraplegic patients under functional electrical stimulation (FES) was studied in vivo using ³¹P NMR. The protocol included rest, 3 min of induced tetanic isometric contraction through surface electrodes and 40 min of recovery. The continuous stimulation, the force recording and the ³¹P NMR measurements were sampled simultaneously inside the whole body imager. Normal values were found for the phosphorous metabolite ratios at rest. During contraction, prominent changes were detected including: a) accumulation of inorganic phosphate (P) accompanied by an unusually strong signal in the phosphomonoester (PME) region, b) phosphocreatine (PCr) decline, and c) a decrease in the intracellular pH. In the following recovery period the physiological state of the muscle was monitored and quantitated by ³¹P NMR. No metabolic and mechanical irreversible damage was detected in the paraplegics' muscles activated by FES under our experimental conditions.     

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability in the Rat

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability inthe Rat. SHU, H., TEITELBAUM, T., WEBB, A. S., MARPLE, L., BRUNCK,B. DEI ROSSI, D., MURRAY, J., AND PAUSTENBACH, D. (1988). Fundam.Appl. Toxicol. 10, 335-343. 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD), an unwanted by-product formed during the manufactureof hexachlorophene and phenoxyherbicides, has been found asan environmental contaminant in many U.S. and Western Europeansites. This study examines in the rat the degree of dermal absorptionof TCDD bound to soil. Such information would assist regulatoryagencies in evaluating the degree of exposure of humans whocome in contact with TCDD-contaminated soil. Several parameterswhich may influence dermal absorption were studied, includingTCDD dose, duration of contact, presence of crankcase oil asa co-contaminant, and environmentally contaminated vs laboratory-preparedsoil. The dermal penetration of TCDD following 4 hr of contactwith skin was approximately 60% of that following 24 hr of contact(P 0.05). Following 24 hr of contact with the skin, the degreeof dermal uptake of TCDD contaminated soil was approximately1% of the administered dose. Under the conditions of the presentstudy, the degree of uptake does not appear to be influencedto any significant extent by the concentration of TCDD on soil,the presence of crankcase oil as co-contaminants, or by environmentallyvs laboratory-contaminated soil. Although a number of parametersexamined in this study did not significantly influence the degreeof dermal absorption of TCDD in the rat following 24 hr of contactwith the contaminated soil, the unqualified use of the 1% valueto estimate human exposure would overestimate human exposure,since there is general agreement among researchers that ratskin tends to be more permeable than human skin to highly lipid-solublecompounds such as TCDD.     

Evidence for the interaction between antacid and gastric mucosa using an "artificial stomach" model including gastric mucosa.

In light of evidence that certain aluminum-based antacids adhere to the gastric mucosa, we modified our previously described "artificial stomach" (AS) model by including a piece of hog stomach and compared the antacid activity of six aluminum-containing antacid products in the model with and without gastric mucosa. The activity of three of these, Maalox, Riopan and Supralox, was not significantly different in the two systems. In contrast, the activity of the other three, Aludrox, Phosphalugel and Simeco, was significantly greater with mucosa. Antacid activity of one product from each set (Supralox, Phosphalugel) was evaluated in two in vivo methods in human volunteers. For both antacids, results in vivo were similar to those obtained with the AS-containing mucosa. Without mucosa, in vivo and in vitro results were dissimilar for Phosphalugel, thus validating the modified AS. The difference between the two sets of antacids can be explained by 1) the fact that the Al:Mg ratio in the set affected by mucosa is greater than that of unaffected antacids, and 2) a weaker antacid load than in unaffected Supralox. We suggest that in an acid milieu, aluminum ions in antacids like Aludrox, Phosphalugel and Simeco are bound to sialic acid residues in mucus glycoproteins, thus retarding the transit of these antacids through both the AS and the real stomach and prolonging their activity in both situations. When the Al:Mg ratio is low or when the amount of antacid salts is large, aluminum ions tend to be buried in complexes, giving them less chance to interact with gastric mucus, so they transit the stomach more quickly.     

The implementation of a knowledge-based pathology Hypertext under HyperCard

A knowledge-based Hypertext of Pathology integrating videodisc-based images and computer-generated graphics with the textual cognitive information of an undergraduate pathology curriculum has been developed. The system described in this paper was implemented under HyperCard⁰⁰ during 1988 and 1989. Three earlier versions of the system that were developed on different platforms are contrasted with the present system. Strengths, weaknesses, and future extensions of the system are enumerated. The conceptual basis and organizational principles of the knowledge base are also briefly discussed.     

A screening assay for detecting CD8+ cell non-cytotoxic anti-HIV responses

The rate of HIV-1 disease progression is influenced by several factors that include pathogen and host genetic variations and the quality of antiviral immune responses. The CD8+ cell non-cytotoxic antiviral response (CNAR) substantially suppresses HIV replication in CD4+ cells and is positively associated with an asymptomatic clinical state. Traditionally, the measurement of CNAR has required several culture procedures and costly reagents. Here we report the development and validation of a screening assay for detection of CNAR that accurately identifies individuals benefiting from this response. Use of the CNAR screening assay should facilitate the evaluation of this important immune parameter in studies of HIV pathogenesis, resistance to infection, and vaccine development.     

Evidence for autosomal recessive inheritance in cerebral gigantism

Three cases of cerebral gigantism, two sibs and their double first cousin, are described in a large inbred family from Israel. Two of the three were observed and diagnosed at birth and two were followed for two years. They all presented the signs and symptoms considered typical of this syndrome, as well as some of the less frequent findings. Generalized oedema and flexion contractures of the feet were observed in two of the three at birth. This has not hitherto been reported in cases of cerebral gigantism, of whom only a few have been observed and diagnosed at birth. Autosomal recessive inheritance is clearly implied in this family.     

Cadmium and the reticuloendothelial system (RES). A specific defect in blood clearance of soluble aggregates of IgG by the liver in mice given cadmium.

The ability of the reticuloendothelial system (RES) to bind and catabolize soluble stable heat aggregates of 125I-IgG (A-IgG) was studied in mice given oral cadmium. Cadmium caused a delay in the circulation clearance of A-IgG in intact animals. The defect was due to impaired liver uptake of A-IgG and correlated with increased liver cadmium. Subsequent catabolism of bound A-IgG by liver slices was not affected. The defect was specific in that clearance of aggregated human serum albumin and colloidal carbon was normal in cadmium mice; this suggests that cadmium may affect either Fc or complement receptors of Kupffer cells in liver.